Peptides containing up to 20 amino acids, some of which are structurally unusual, are produced by bacteria and fungi by way of their secondary metabolism using non ribosomal peptide synthetases. Many of the secondary metabolites having a peptide structure which are thus far known possess interesting biological effects as antibiotics, enzyme inhibitors, cardiotonics, immunomodulators, insecticides, nematocides, etc. (see, for example, Grafe, U. Biochemie der Antibiotika (Biochemistry of the Antibiotics), Spektrum Heidelberg, 1992).
Within the structural class of the peptide active compounds, what are termed the peptaibols are distinguished by the fact that they contain an unusually large number of amino acids (up to 20) including a high proportion of alpha-aminobutyric acid (Brückner, H., König, W. A., Greiner, M., Jung, G. Angew. Chern. Int. Ed. Engl. 18 (1979), 476–477). Furthermore, peptaibols are frequently acetylated at the N terminus and have a residue containing an alcohol group (e.g. phenylalaninol) or an aldehyde group at the C terminus.
The mode of action of the peptaibols is generally assumed to be the formation of pores in biological membranes (M. K. Das et al., Biochemistry, 25, 7110–7117, 1986). As a result, ions can penetrate into the cell in an uncontrolled manner and interfere with the vital biochemical processes, something which could explain the antibiotic effect of many peptaibols. In addition to the antibiotic effect, various peptaibols have been observed to have other biological effects which are different. Ampullosporins induce pigment formation in Phoma destructiva and produce neuroleptic effects in the mouse (WO99/12598; DE199148644; M. Ritzau et al. J. Antibiotics 50, 722–728,1997; Kronen et al., J. Antibiotics, 54,175–178,2001). While bergofungin components (A. Berg et al. J. Antibiotics 52, 666–669, 1999) inhibit prolylendopeptidase in submicromolar concentrations, they have no effects on Phoma destructiva. Clonostachin (T. Chikanishi et al, J. Antibiotics, 50, 105–110, 1997) inhibits platelet aggregation. The antiviral peptaivirins A and B (B. S. Yun et al. Tetrahedron Letters, 41, 1429–1431,2000) have recently been described. It is not possible to provide any uniform explanation for, and prediction of, the biological activities of the various peptaibols because of the differences in the structures of these compounds.
The cephaibols, which are composed linearly of 16 or 17 amino acids or amino acid derivatives, some of which are not encodable, constitute another group of the peptaibol antibiotics. The structure, preparation and biological activities of the cephaibols are described, for example, in WO 00/68256 or M. Schiell et al., J. Antibiotics, 54 (2001) 220–233. Cephaibols have inhibitory effects on endoparasites and/or ectoparasites (as described in U.S. Pat. No. 6,582,949) which are pathogenic to humans and/or animals, such as trematodes, nematodes, arachnida and some insects. In addition to this, the cephaibols exhibit antibacterial activities.
Cephaibols are not known to have any other therapeutic uses.